Therapeutic dendritic-cell vaccine for chronic HIV-1 infection.
Nature medicine 2004 Dec 1; 10(12):1359-65
Lu W W, Arraes L LC, Ferreira W WT, Andrieu J JM
Institut de Recherche sur les Vaccins et l'Immunothérapie des Cancers et du Sida, Laboratoire d'Oncologie et Virologie Moléculaire, Faculté de Médecine René Descartes, Centre Biomédical des Saints-Pères, Université Paris 5, France. louis.wei-lu@ir
We present the results of a preliminary investigation of the efficacy of a therapeutic dendritic cell (DC)-based vaccine for HIV-1. We immunized 18 chronically HIV-1-infected and currently untreated individuals showing stable viral loads for at least 6 months with autologous monocyte-derived DCs loaded with autologous aldrithiol-2-inactivated HIV-1. Plasma viral load levels were decreased by 80% (median) over the first 112 d following immunization. Prolonged suppression of viral load of more than 90% was seen in 8 individuals for at least 1 year. The suppression of viral load was positively correlated with HIV-1-specific interleukin-2 or interferon-gamma-expressing CD4(+) T cells and with HIV-1 gag-specific perforin-expressing CD8(+) effector cells, suggesting that a robust virus-specific CD4(+) T-helper type 1 (T(H)1) response is required for inducing and maintaining virus-specific CD8(+) effectors to contain HIV-1 in vivo. The results suggest that inactivated whole virus-pulsed DC vaccines could be a promising strategy for treating people with chronic HIV-1 infection.